PROJECT-004: MOLECULAR CARCINOGENESIS AND CHEMOPREVENTION PROGRAM (MCC) PROJECT SUMMARY / ABSTRACT The Molecular Carcinogenesis and Chemoprevention (MCC) Program, led by Steven K. Clinton, MD, PhD, has a collaborative team of 37 basic, translational and clinical scientists. These faculty have appointments in 17 Departments/Divisions within the Colleges of Medicine, Arts and Sciences, Pharmacy, Food Agriculture and Environmental Sciences, Public Health, Dentistry, Education and Human Ecology and Veterinary Medicine. The Specific Aims of the MCC Program are: 1) to characterize molecular and cellular changes induced by chemical, physical, hormonal and infectious agents that contribute to neoplastic transformation and multistage carcinogenesis in experimental models and humans; 2) to develop and characterize novel agents for cancer chemoprevention and define their efficacy, safety, and mechanisms of action using in vitro and preclinical models; and 3) to identify dietary and nutritional components that may enhance or inhibit the carcinogenesis cascade across the continuum of cancer progression. Each of these aims results in translational prevention studies in human populations with an emphasis on those at risk due to exposure to carcinogenic or cancer promoting agents, familial and genetic predisposition, or due to the presence of premalignant lesions. The MCC Program's overarching goals, implemented through multiple MCC initiatives, are to accelerate the research objectives of each Aim through incentivizing and stimulating collaborative investigation among MCC members, other investigators of the OSUCCC as well as facilitating the implementation of translational studies of cancer etiology, prevention, and progression in human trials. The MCC enhances quality by promoting knowledge of and utilization of state-of-the-art technologies provided by the OSUCCC shared resources (members utilize 14/14 shared resources). The MCC Program, during its previous review (2004-2009) was graded as ?Outstanding to Exceptional?. During this funding period (2009-2014), MCC Program members published 484 cancer relevant peer-reviewed articles in top tier journals for the respective fields of carcinogenesis, chemoprevention, and nutrition. Collaboration is extensive with 28% intra-programmatic publications and 55% inter-programmatic publications, with 272 or 56% being multi-institutional and 447 or 92% being collaborative publications. Peer-reviewed funding for the MCC Program is $5.19M in annual direct costs with $2.9M (56%) from the NCI. Translational research has been robust as well with 20 human trials led by MCC members employing the OSUCCC Clinical Trials Office resulting in 360 interventional accruals during the last funding cycle, 72% of which were from investigator-initiated Phase I and II trials. The current MCC Program uniquely integrates investigators across disciplines yet with shared interests focusing upon the interactive themes of carcinogenesis, chemoprevention, and nutrition. Our future goals include the integration of new initiatives involving the microbiome and metabolomics, two areas benefiting from rapid growth in technology and bioinformatics that will dramatically impact our understanding of carcinogenesis and strategies for cancer prevention.